The molecular basis of chromosome replication has not yet been elucidated. Although numerous information has been collected in enzymes and compounds involved in DNA metabolism, biochemical processes in the gene duplication in a semiconservative manner have not been reproduced in vitro. This difficulty is mostly due to a lack of the established system in vitro to investigate the problems in DNA replication in spite of the fact that the structure and function of the individual enzymes and genetics in the process of DNA metabolism have been strongly studied. The detailed mechanism of known enzymes and the search for new proteins in these processes will be investigated. Emphasis will be placed on the use of mutants defective in DNA metabolism and known enzymes to identify and characterize the new enzymatic reactions responsible for the molecular events during chromosome replication.